The role of the lymphatic system in the absorption and distribution of free and liposome-entrapped antitumor agents (adriamycin, ara-C and melphalan) administered to rats and to tumor-bearing monkeys by ip, iv or sc routes is under investigation. Liposomal encapsulation markedly altered many pharmacological properties, such as tissue distribution, metabolism and excretion, of the drugs tested; entrapment in liposomes also produced a significant increase in their lymphatic absorption and lymph node uptake. The antitumor effect of melphalan against lymph node metastasis of mammary adenocarcinoma 13762 was enhanced by liposomal encapsulation. Studies in progress are aimed at optimizing liposome characteristics (e.g., size, charge and lipid composition) for maximal lymph node uptake and retention and for maximal chemotherapeutic activity, and attempts are underway to target liposomes to specific sites, such as the lymph nodes, using monoclonal antibodies coupled to the liposome membrane.